January – Dunstable Priory falls prey to Henry VIII of England's Dissolution of the Monasteries.
January 6 – King Henry VIII of England marries Anne of Cleves, his fourth Queen consort.
February 14 – Charles V, Holy Roman Emperor, enters Ghent without resistance and executes rebels.
March – Waltham Abbey is the final priory to fall prey to the Dissolution of the Monasteries.
May 17 - Sher Shah Suri defeats and deposes Mughal Emperor Humayan at the Battle of Kannauj, establishing the Sur Empire.
July 7 – Coronado captures Hawikuh, at this time known as part of Cíbola, but fails to find the legendary gold.
July 9 – King Henry VIII of England divorces Anne of Cleves, his fourth Queen consort.
July 28 – One of the most important political figures of the reign of Henry VIII of England, Thomas Cromwell, is executed on order from the king on charges of treason. Henry marries his fifth wife, Catherine Howard, on the same day.
Early September – Gibraltar is sacked by the fleet of Barbary pirate Ali Hamet, a Sardinian renegade in the service of the Ottoman Empire, and many of the leading citizens taken as captives to Peñón de Vélez de la Gomera in Morocco. This leads to construction of the defensive Charles V Wall, at this time known as the Muralla de San Benito.
September 3 – Gelawdewos succeeds his father Lebna Dengel as Emperor of Ethiopia.
September 27 – The Society of Jesus (Jesuits) is approved by Pope Paul III, in his bull Regimini militantis Ecclesiae.
October 1 – Battle of Alborán: A Habsburg Spanish fleet under the command of Bernardino de Mendoza destroys an Ottoman fleet commanded by Ali Hamet off Alborán Island in the Mediterranean.
October 18 – An expedition led by Spanish conquistador Hernando de Soto destroys the fortified village of Mabila in modern-day Alabama, killing paramount chief Tuskaloosa.
Antwerp is besieged for three days by Maarten van Rossum.
Georg Joachim Rheticus publishes De libris revolutionum Copernici narratio prima in Danzig, an abstract of Copernicus' as yet unpublished De revolutionibus orbium coelestium and the first printed publication of Copernican heliocentrism.
Europe is hit by a heat wave and drought lasting for about 7 months. Rivers such as the Rhine and Seine dry up and many people die from dysentery and other illnesses caused by lack of safe drinking water. However, this year's vintage from Würzburger Stein and other vineyards is particularly notable.
Martin Luther expels the theologian Caspar Schwenckfeld from Silesia.
Paracelsus visits Villach.
approximate date – The musket is introduced into Japan from Europe.
January 18 – Catherine, Duchess of Braganza, Claimant to the Portuguese throne in 1580 (d. 1614)
January 24 – Edmund Campion, English Jesuit and Roman Catholic martyr (d. 1581)
January 28 – Ludolph van Ceulen, German mathematician (d. 1610)
February 12 – Won Gyun, Korean general and admiral during the Joseon Dynasty (d. 1597)
February 23 – Hedwig of Brandenburg, Duchess of Brunswick-Wolfenbüttel (d. 1602)
February 25 – Henry Howard, 1st Earl of Northampton, English aristocrat and courtier (d. 1614)
March 1 – Enrique de Guzmán, 2nd Count of Olivares, Spanish noble (d. 1607)
March 17 – Bernhard VII, Prince of Anhalt-Zerbst, German prince of the House of Ascania (d. 1570)
April 3 – Maria de' Medici, Italian noble (d. 1557)
April 8 – Toyotomi Hidenaga, Warlord (d. 1591)
May 9 – Maharana Pratap, Indian warrior king, 1500s (d. 1597)
Paolo Paruta, Italian historian (d. 1598)
Bartholomäus Scultetus, mayor of Görlitz, astronomer (d. 1614)
May 22 – James, Duke of Rothesay, Scottish prince (d. 1541)
May 24 – Paschal Baylon, Spanish friar (d. 1592)
May 31 – Henry Cheyne, 1st Baron Cheyne, English politician and Baron (d. 1587)
June 3 – Charles II, Archduke of Austria, regent of Inner Austria (d. 1590)
June 9 – Shima Sakon, Samurai (d. 1600)
June 11 – Barnabe Googe, English poet (d. 1594)
June 29 – Ana de Mendoza, Princess of Eboli, Spanish countess (d. 1592)
June 30 – Countess Palatine Elisabeth of Simmern-Sponheim, Duchess of Saxony (d. 1594)
July 7 – John Sigismund Zápolya, King of Hungary (d. 1571)
July 11 – Adolf of Nassau, Count of Nassau, Dutch soldier (d. 1568)
July 16 – Alfonso Carafa, Italian cardinal (d. 1565)
July 19 – Ludowika Margaretha of Zweibrücken-Bitsch, spouse of Count Philip V of Hanau-Lichtenberg (d. 1569)
August 4 – Sisto Fabri, Italian theologian (d. 1594)
August 5 – Joseph Justus Scaliger, French Protestant scholar (d. 1609)
August 25 – Lady Catherine Grey, English noblewoman, potential successor to the throne (d. 1568)
August 26 – King Magnus of Livonia (d. 1583)
September 5 – Magnus, Duke of Holstein, Prince of Denmark (d. 1583)
September 9 – John VII, Count of Oldenburg (d. 1603)
October 1 – Johann Jakob Grynaeus, Swiss Protestant clergyman (d. 1617)
November 12 – Anna of Veldenz, Margrave of Baden (d. 1586)
November 16 – Princess Cecilia of Sweden (d. 1627)
December 8 – Giovanni Vincenzo Gonzaga, Roman Catholic cardinal (d. 1591)
December 21 – Thomas Schweicker, German artist (d. 1602)
December 28 – Charles I, Duke of Mecklenburg (d. 1610)
December 31 – Silvio Antoniano, Catholic cardinal (d. 1603)
December 21 – Man Singh I, Mughal noble (d. 1614)
Andrea Andreani, Italian wood engraver (d. 1623)
Francis Drake, English sea captain, privateer, navigator, slaver, pirate and politician (d. 1596)
Christopher Hatton, English politician (d. 1591)
George Hastings, 4th Earl of Huntingdon, English nobleman (d. 1604)
Pierre Jeannin, French statesman (d. 1622)
François Viète, French mathematician (d. 1603)
Amago Yoshihisa, Japanese samurai and warlord (d. 1610)
William Byrd, English composer (d. 1623)
Bernardino de Mendoza, Spanish military commander (d. 1604)
January 27 – Angela Merici, Italian religious leader and saint (b. 1474)
March 30 – Matthäus Lang von Wellenburg, German statesman and archbishop of Salzburg (b. 1469)
May 6 – Juan Luís Vives, Spanish scholar (b. 1492)
May 22 – Francesco Guicciardini, Italian statesman and historian (b. 1483)
July 28 – Thomas Cromwell, 1st Earl of Essex, English statesman (executed) (b. c.1485)
Thomas Abel, English priest (martyred) (b. c. 1497)
Robert Barnes, English reformer (martyred) (b. 1495)
August 23 – Guillaume Budé, French scholar (b. 1467)
August 24 – Girolamo Francesco Maria Mazzola (Parmigianino), Italian artist (b. 1503)
August 28 – Federico II Gonzaga, Duke of Mantua (b. 1500)
September 2 – Lebna Dengel, Emperor of Ethiopia (in battle) (b. 1501)
October 5 – Helius Eobanus Hessus, German Latin poet (b. 1488)
date unknown – Francisco de Ulloa, Spanish explorer
Elizabeth Blount, mistress of Henry VIII of England (b. 1502)
Tristão da Cunha, Portuguese explorer (b. 1460)
Johann Georg Faust, German alchemist (b. 1480)
Year 1540 (MDXL) was a leap year starting on Thursday (link will display the full calendar) of the Julian calendar.